O'Conner S E, Imperiali B
Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena 91125, USA.
Chem Biol. 1998 Aug;5(8):427-37. doi: 10.1016/s1074-5521(98)90159-4.
Asparagine-linked glycosylation has the capacity to greatly influence the structure and function of glycoproteins. In most cases, however, it is unclear specifically how the carbohydrate moiety interacts with the protein to influence its conformation.
A series of glycosylation based on the critical A285 glycosylation site of the hemagglutinin glycoprotein from influenza from influenza virus was used as a model system to study the effects of asparagine-linked glycosylation. Derivatization of this peptide with a family of short carbohydrates reveals that subtle changes in the structure of the carbohydrate have a dramatic impact on peptide conformation. Modification of the hemagglutinin glycopeptide with a truncated version of the native carbohydrate induces a beta-turn structure similar to the structure found in the native protein. Replacement of the C2 and C2' N-acetyl groups of the carbohydrates with hydroxyl moieties results in a less well-ordered peptide conformation.
It is likely that the N-acetyl groups of the carbohydrates have a critical role in promoting the more compact beta-turn conformation through steric interactions with the peptide. This study has demonstrated that relatively small changes in carbohydrate composition can have dramatic ramifications on glycopeptide conformation.
天冬酰胺连接的糖基化能够极大地影响糖蛋白的结构和功能。然而，在大多数情况下，尚不清楚碳水化合物部分具体如何与蛋白质相互作用以影响其构象。
以流感病毒血凝素糖蛋白的关键A285糖基化位点为基础的一系列糖基化被用作模型系统，以研究天冬酰胺连接的糖基化的影响。用一族短碳水化合物对该肽进行衍生化显示，碳水化合物结构的细微变化对肽的构象有显著影响。用天然碳水化合物的截短版本对血凝素糖肽进行修饰会诱导出一种类似于天然蛋白质中发现的β-转角结构。用羟基部分取代碳水化合物的C2和C2' N-乙酰基会导致肽构象的有序性降低。
碳水化合物的N-乙酰基可能通过与肽的空间相互作用在促进更紧密的β-转角构象方面起关键作用。这项研究表明，碳水化合物组成中相对较小的变化可能对糖肽构象产生重大影响。
